Kallikrein-related peptidase genes as promising biomarkers for prognosis and monitoring of human malignancies

Abstract

Tissue kallikrein (KLK1) and the kallikrein-related peptidase (KLK2-15) genes encode for a subgroup of 15 homologous secreted serine proteases possessing numerous physiological roles, such as the regulation of blood pressure, hormone processing and tissue remodeling. The expression of KLKs is detected in a broad spectrum of human tissues where it has been found to be regulated mainly by steroids hormones. The aberrant expression of KLKs, presented in many human malignancies, highlights the significance of this gene family for early diagnosis, prognosis and monitoring of cancer patients, as it is strongly emphasized by the routine use of PSA (KLK3) for prostate cancer management. Here, we review the presently known data regarding the role of KLKs as cancer biomarkers, giving emphasis on novel information about the subject.

Kallikrein-related peptidases in prostate, breast, and ovarian cancers: from pathobiology to clinical relevance

“…In fact, PSA/KLK3 serum concentration is an excellent marker for the supervision of the treatment success (Avgeris et al , 2010 ). Serum PSA/ KLK3 levels are signifi cantly decreased after treatment (radical prostatectomy, androgen exclusion, radiotherapy, or chemotherapy) below the analytical assays ' detection limit, due mainly to the restriction of the prostate gland, indicating in this way the treatment course success.…”

“…On the contrary, KLK9 , KLK13 , and KLK15 mRNA expression has been correlated with a more favorable outcome for breast cancer patients (Avgeris et al , 2010 ;Mavridis and Scorilas , 2010 ). KLK10 occupies a distinctive place in clinical breast cancer research because it has been described as an important tumorsuppressor gene.…”

“…Bearing in mind the irreversible impact of proteases upon their substrates, as well as the launch of downstream enzyme cascades that lead to the amplifi cation of the initial stimuli, the regulation of KLKs activity becomes crucial for their benefi cial physiological function. An enormous amount of evidence highlights the abnormal regulation of KLKs in cancer, in terms of KLKs gene expression, as well as KLKs synthesis, secretion, and activation Emami and Diamandis , 2007 ;Mavridis and Scorilas , 2010 ), and reveals also their diagnostic and prognostic clinical exploitation (Obiezu and Diamandis , 2005 ;Paliouras et al , 2007 ;Avgeris et al , 2010 ;Mavridis and Scorilas , 2010 ). This deregulation is more evident and further studied in endocrine-related tumors -a fact which can be partially explained by the transcriptional control of KLKs by steroid hormones.…”

Human kallikrein 4 signal peptide induces cytotoxic T cell responses in healthy donors and prostate cancer patients

“…An array of kallikrein family members are overexpressed in hormone-dependent cancers and many are associated with disease progression and poor prognosis [11,42] Table 2 -KLK4A specific CTL responses in healthy donors and prostate cancer patients. Induction of KLK4A-specific CTL was analyzed using a KLK4A/HLA-A*0201-specific pentamer from whole PBMC (precursor frequency, PF) or after a number of restimulations which gave the maximum response (varied between donors, most commonly 3-4 restimulations).…”

Targeting Free Prostate-Specific Antigen forIn VivoImaging of Prostate Cancer Using a Monoclonal Antibody Specific for Unique Epitopes Accessible on Free Prostate-Specific Antigen Alone

“…4. 15,16 PSA released into the blood is noncatalytic, in part due to inactivation subsequent to the formation of stable covalent complexes with major extracellular protease inhibitors, particularly a-1-antichymotrypsin (SERPINA3 or ACT), although reactions with a-2-macroglobulin (A2M) are faster, at least in vitro. 17,18 A smaller percentage (5%-40%) of the noncatalytic PSA in the blood occurs as free, unbound forms (free PSA [fPSA]) that are unable to form complexes with, for example, ACT or A2M despite & 10…”